Dihydroergotamine (DHE) is an ergot alkaloid that was identified as an effective treatment for migraine nearly fifty years ago (Raskin, Neurology 36:995–997 (1986); Silberstein, et al., Headache 30:334–339 (1990); Saadah, Headache 32:18–20 (1992); and Winner, Headache 33:471–475 (1993)). It is presently marketed both as an injectable product (DHE 45®) and as a nasal spray (Migranal®). DHE is typically administered by intramuscular or intravenous injection (Belgrade, et al., Neurology 39:590–592 (1989); Winner, Headache 33:471–475 (1993)), but it is also effective when given subcutaneously (Klapper, et al., Headache 32:21–23 (1992); Winner, et al., Arch. Neurol. 53:180–184 (1996); and Becker, et al., Headache 36:144–148 (1996)).
Although effective in the treatment of migraine, DHE administration is often accompanied by side effects such as nausea, vomiting and chest pain (Winner, et al., Arch. Neurol. 53:180–184 (1996)). At least one side effect, nausea, occurs more frequently after intravenous administration than after intramuscular or intranasal administration. When given subcutaneously at a concentration of only 1.5 mM, DHE has been reported to cause nausea in nearly 16% of treated patients (Winner, et al., Arch. Neurol. 53: 80–184 (1996)). New drug formulations and methods for administering DHE which reduce its adverse side effects would represent a significant advance in migraine therapy.